title: Oatp58Dc contributes to blood-brain barrier function by excluding organic anions from the Drosophila brain.
abstract: The blood-brain barrier (BBB) physiologically isolates the brain from the blood and, thus, plays a vital role in brain homeostasis. Ion transporters play a critical role in this process by effectively regulating access of chemicals to the brain. Organic anion-transporting polypeptides (Oatps) transport a wide range of amphipathic substrates and are involved in efflux of chemicals across the vertebrate BBB. The anatomic complexity of the vascularized vertebrate BBB, however, creates challenges for experimental analysis of these processes. The less complex structure of the Drosophila BBB facilitates measurement of solute transport. Here we investigate a physiological function for Oatp58Dc in transporting small organic anions across the BBB. We used genetic manipulation, immunocytochemistry, and molecular techniques to supplement a whole animal approach to study the BBB. For this whole animal approach, the traceable small organic anion fluorescein was injected into the hemolymph. This research shows that Oatp58Dc is involved in maintaining a chemical barrier against fluorescein permeation into the brain. Oatp58Dc expression was found in the perineurial and subperineurial glia, as well as in postmitotic neurons. We specifically targeted knockdown of Oatp58Dc expression in the perineurial and subperineurial glia to reveal that Oatp58Dc expression in the perineurial glia is necessary to maintain the barrier against fluorescein influx into the brain. Our results show that Oatp58Dc contributes to maintenance of a functional barrier against fluorescein influx past the BBB into the brain.
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Seabrooke
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Donnell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D019793:Fluorescein / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation; D006458:Hemolymph / Q000378:metabolism; D017136:Ion Transport; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D000838:Anions; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; C584034:Oatp58Dc protein, Drosophila; D027361:Organic Anion Transporters; D019793:Fluorescein
keywords: Drosophila; fluorescein; organic anion-transporting polypeptide; perineurial; subperineurial